Molecular competition between plasminogen activator inhibitors type -1 and -2 for urokinase: Implications for cellular proteolysis and adhesion in cancer

Date

2011

Authors

Lobov, Sergey
Ranson, Marie

Journal Title

Journal ISSN

Volume Title

Publisher

Elsevier

Abstract

Up-regulation of the urokinase plasminogen activation (uPA) system leads to increased cancer invasion and metastasis. Plasminogen activator inhibitors type-1 (PAI-1/SERPINE1) and type-2 (PAI-2/SERPINB2) have similar uPA inhibitory properties yet PAI-1 promotes cell invasion by modulating cell adhesion and migration. High tumour PAI-2 levels are associated with improved prognoses. Herein we show that PAI-2 is capable of inhibiting uPA in the presence of PAI-1, particularly on adherent cells in the presence of vitronectin. This suggests that elevated levels of PAI-2 in the tumour microenvironment could outcompete PAI-1 for uPA inhibition through its inhibitory serpin function. However, PAI-1 modulated cell adhesion in a largely uPA-independent manner consequently PAI-2 could not counteract the effects of PAI-1 on adhesion/migration. Thus studies aimed at further characterising the interplay between PAI-1 and PAI-2 on uPA-dependent pro-invasive processes are warranted.

Description

Keywords

Keywords: plasminogen activator inhibitor 1; plasminogen activator inhibitor 2; serine proteinase inhibitor; urokinase; vitronectin; article; cell adhesion; cell migration; controlled study; enzyme inhibition; human; human cell; malignant neoplastic disease; molecu Adhesion; Migration; PAI-1/SERPINE1; PAI-2/SERPINB2; Urokinase

Citation

Source

Cancer Letters

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.1016/j.canlet.2011.01.018

Restricted until

2037-12-31